To date, nearly all in vitro studies examining the role of membrane depolarization on spiral ganglion neuron (SGN) survival have used chronic depolarization as a model. These studies demonstrated the requirement of cytosolic Ca2+ for the neurotrophic effects of depolarization; however, chronic depolarization is an imperfect model of physiological neural activity, which occurs as patterns of brief bursts of depolarization. There is accumulating evidence that different patterns of Ca2+ oscillations result in different patterns of intracellular signaling. Moreover, under conditions of chronic depolarization only a single voltage-gated Ca2+ channel (the L-type channel) is open, while others are inactivated. This suggests that the signaling pathways activated by chronic depolarization and patterned activity may differ. In the present study I test this by examining the effect of patterned activity on SGN survival, determine how these patterns modulate cytosolic Ca2+, and identify the signaling pathways that promote SGN survival. These studies will identify pathways involved with activity-dependent SGN survival. The result will allow the correlation of electrical stimulation patterns used in cochlear implants with their long-term effects on SGN survival in vivo.